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Abstract Background As a response to the political decision by the Norwegian Ministry of Health and Care Services to establish some kind of “medication free treatment” for patients with severe mental illness throughout the country, a 6-bed ward unit dedicated to offer such treatment was in 2017 established in Tromsø, Norway by the North Norway Health Care Region. The aim of the present study was to explore the experiences of patients admitted to this ward unit. Method Semi-structured interviews were conducted with 19 persons who had received treatment from the ward during the period January 2017 to October 2021. Analysis was done in line with Systematic Text Condensation and interviews were recorded, transcribed and analyzed using software NVivo. Results The importance of engaging in a dialogue about the possibilities of living a life without medication was unanimously validated, along with a focus on empowerment, motivation, activity and flexibility. Not everyone reported fulfillment of their own wishes or the ward’s goal of tapering down, and reflected upon emotions such as ambivalence or fear. Three core concepts were identified to describe the participants’ experiences: 1) Tapering off, 2) Relations, and 3) Frames and content. A fourth concept overarches the process formed by these concepts; 4) Processes across categories. Conclusion The study contributes to a deeper understanding of what "medication free" truly means, going beyond simply taking or not taking medications. It adds nuance to the debate surrounding medication free treatment. The ability to taper off medications is linked to intrapersonal factors, such as readiness and personal commitment, as well as the therapeutic environment, including the frames and values present on the ward. "Medication free" is more complex than it may initially appear, as many participants continue to use some form of psychotropic drugs. The sense of being part of something new and "exclusive" can be understood in light of what participants felt was lacking in previous treatment. It appears to be a need of rediscovering the significance of empowerment and empathic relationships in treatment of severe mental illness, in order to foster a sense of coherence and meaning.

Abstract Background In January 2017, the Norwegian government mandated the establishment of an inpatient unit for “medication-free treatment” for patients with severe mental illness at the University Hospital of North Norway in Tromsø. This study aims to explore the employees’ experiences with this unit. Method Focus group interviews were conducted October 2021 – February 2022. For analysis, the participants were divided into three groups; S (staff working at the medication-free unit), M (people involved in management at the unit) and T (therapists working elsewhere in the hospital). The analysis followed the Systematic Text Condensation and interviews were recorded, transcribed and analysed using NVivo software. Results Health professionals described their experiences with medication-free treatment through five main concepts: 1) Employees’ motivation; 2) Frames; 3) Network; 4) Relations; and 5) Patients’ motivation. Staff and management expressed strong motivation for an alternative to “treatment as usual,” focusing more on recovery and relationships than on the absence of medication. Therapists from other hospital areas highlighted resource allocation concerns and expressed a desire to learn from the unit. Challenges were acknowledged by all groups. Conclusion The term “medication-free treatment’’ might be misleadning. While patiens at the unit can use medications, there is a strong emphasis on patient autonomy and the option to taper off medication and live a life without them. The study adds valuable knowledge about the the experiences of employees working at a medication-free unit, and provides insights into the complexity of treating severe mental illness, both with and without medication. It highlights the importance of sufficient time, stability and resources to focus on each patient’s strengths and challenges. All employees agree that tailored measures in long-term treatment and a clear focus on recovery should be integral, even without an emphasis on “medication-free treatment”.

Abstract Background This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. Methods This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants’ experiences, thoughts, expectations and attitudes. Results The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. Conclusion This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.

Abstract Background A focus on patient’s and service user’s perspectives regarding long-term antipsychotic treatment led to a declaration from the Norwegian Ministry of Health in 2015 to offer treatment without psychotropic medication in mental health as a voluntary option in all four health care regions. In the northernmost region, a 6-bed inpatient ward unit was established, uniquely designed to give people with severe mental illness the possibility to choose such treatment. Only voluntary admissions were accepted. The aim of the present study was to explore the motivation for applying for medication free treatment among patients with several years of treatment history due to psychosis. Method We performed nineteen semi-structured, in-depth interviews with persons having at least one admission at the medication free treatment ward during the period 01.01.17 – 17.10.2021. The interviews were recorded, transcribed and analysed using computer-assisted qualitative data analysis software (NVivo). Systematic Text Condensation was applied, with analysis of data from the first interview. Exploration of connections, similarities and nuances was performed through axial coding with continuous comparison of data and memo writing, followed by focused coding identifying core concepts. Results All participants had a diagnosis of severe mental illness and a history of use of antipsychotics throughout many years. The motivation to apply for medication free treatment was complex. Negative experiences with medication were described, but also positive. Many had tried to taper off before, but described this as a lonely and difficult process. Five core concepts were formed and developed from the participants’ narratives: 1) Medication experiences, 2) Developing illness, 3) Treatment in general, 4) Social life and 4) Growing up. Conclusion The concept of medication free treatment represents a salutogenetic hope for change, closely linked to self-efficacy and an experience of mastery. Potential conflicts concerning guidelines or evidence on medication does not come forward as important. Support from family and professionals is crucial, in contrast to the feeling of being alone when hoping for change. Motivational factors are closely linked to the concept of recovery, where interaction happens on both an individual and a structural level.

Abstract Classical metalation reactions such as the metal-halogen exchange have had a transformative impact on organic synthesis owing to their broad applicability in building carbon-carbon bonds from carbon-halogen bonds. Extending the metal-halogen exchange logic to a metal-carbon exchange would enable the direct modification of carbon frameworks with new implications in retrosynthetic analysis. However, such a transformation requires the selective cleavage of highly inert chemical bonds and formation of stable intermediates amenable to further synthetic elaborations, hence its development has remained considerably challenging. Here we introduce a skeletal metalation strategy that allows lactams, a prevalent motif in bioactive molecules, to be readily converted into well-defined, synthetically useful organonickel reagents. The reaction features a selective activation of unstrained amide C–N bonds mediated by an easily prepared Ni(0) reagent, followed by CO deinsertion and dissociation under mild room temperature conditions in a formal carbonyl-to-nickel-exchange process. The underlying principles of this unique reactivity are rationalized by organometallic and computational studies. The skeletal metalation is further applied to a direct CO excision reaction and a carbon isotope exchange reaction of lactams, underscoring the broad potential of metal-carbon exchange logic in organic synthesis.

Ariesanti Tri Handayani,1 Clara Valentina,1 I Gusti Ayu Ratna Suryaningrum,1 Putu Dian Megasafitri,1 I Gusti Ayu Made Juliari,1 Ida Ayu Ary Pramita,1 Shintaro Nakayama,2,3 Eisuke Shimizu,2,3 Anak Agung Mas Putrawati Triningrat1 1Ophthalmology Study Program Faculty of Medicine, Udayana University, Denpasar, Bali, Indonesia; 2Department of Ophthalmology, Keio University School of Medicine, Shinjuku, Tokyo, Japan; 3OUI Inc ., Minato, Tokyo, JapanCorrespondence: Ariesanti Tri Handayani, Ophthalmology Study Program Faculty of Medicine, Udayana University, Jl. Diponegoro, Dauh Puri Klod, Kec, West Denpasar, Denpasar City, Bali, 80113, Indonesia, Tel +62818-375611, Email ariesanti@unud.ac.idIntroduction: Dry eye disease (DED) is a multifactorial disease of tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability leading to decrease of vision, productivity and quality of life, and blindness. DED diagnosis remains difficult and underdiagnosed regarding inconsistency between subjective symptoms and clinical findings. Tear break-up time (TBUT) is an objective indicator of tear film stability in diagnostic DED. A novel smartphone attachment, namely SEC (smart eye camera), could mimic conventional slit lamp to assess TBUT and beneficial in facilitating DED diagnosis. Reliability between a non and an ophthalmologist in TBUT assessment and DED diagnosis is observed in this study.Purpose: To determine interobserver reliability of TBUT measurement for diagnosing DED using SEC.Design: This a cross-sectional analytic study involving 99 participants (198 eyes) aged 40 years who visited Pratama Gema Santi Hospital, Nusa Penida, from September 2nd to 4th, 2022, with consecutive sampling technique.Methods: Fluoresceined eyes were filmed using the SEC device and apps, continued by masked ophthalmologist and resident assessing TBUT based on the video. The primary outcome is interobserver reliability for TBUT measurement and DED diagnosis.Results: The mean age of participants was 55.22± 9.78 years, 48.5% male and 51.5% female. The reliability of interobserver in assessing DED based on TBUT test is 0.78 (95% CI=0.31– 1.26, P-value=0.001), and interobserver reliability in diagnosing DED based on OSDI and TBUT showed good agreement (weighted kappa=0.71). Good interobserver reliability underscores that non-ophthalmologists can diagnose DED based on TBUT video using SEC.Conclusion: SEC video has good interobserver reliability to assess TBUT for DED diagnosis. SEC can be used as one of the methods in assessing DED in limited health care facilities. The high reliability of interobserver assessment indicates that DED diagnosis using video taken with SEC may be useful for telemedicine evaluation in remote areas.Graphical Abstract: Keywords: dry eye disease, smart eye camera, telemedicine

Autophagy engulfs cellular components in double-membrane-bound autophagosomes for clearance and recycling after fusion with lysosomes. Thus, autophagy is a key process for maintaining proteostasis and a powerful cell-intrinsic host defense mechanism, protecting cells against pathogens by targeting them through a specific form of selective autophagy known as xenophagy. In this context, ubiquitination acts as a signal of recognition of the cargoes for autophagic receptors, which direct them towards autophagosomes for subsequent breakdown. Nevertheless, autophagy can carry out a dual role since numerous viruses including members of the Orthoherpesviridae family can either inhibit or exploit autophagy for its own benefit and to replicate within host cells. There is growing evidence that Herpes simplex virus type 1 (HSV-1), a highly prevalent human pathogen that infects epidermal keratinocytes and sensitive neurons, is capable of negatively modulating autophagy. Since the effects of HSV-1 infection on autophagic receptors have been poorly explored, this study aims to understand the consequences of HSV-1 productive infection on the levels of the major autophagic receptors involved in xenophagy, key proteins in the recruitment of intracellular pathogens into autophagosomes. We found that productive HSV-1 infection in human neuroglioma cells and keratinocytes causes a reduction in the total levels of Ub conjugates and decreases protein levels of autophagic receptors, including SQSTM1/p62, OPTN1, NBR1, and NDP52, a phenotype that is also accompanied by reduced levels of LC3-I and LC3-II, which interact directly with autophagic receptors. Mechanistically, we show these phenotypes are the result of xenophagy activation in the early stages of productive HSV-1 infection to limit virus replication, thereby reducing progeny HSV-1 yield. Additionally, we found that the removal of the tegument HSV-1 protein US11, a recognized viral factor that counteracts autophagy in host cells, enhances the clearance of autophagic receptors, with a significant reduction in the progeny HSV-1 yield. Moreover, the removal of US11 increases the ubiquitination of SQSTM1/p62, indicating that US11 slows down the autophagy turnover of autophagy receptors. Overall, our findings suggest that xenophagy is a potent host defense against HSV-1 replication and reveals the role of the autophagic receptors in the delivery of HSV-1 to clearance via xenophagy.

IntroductionThe European Union has recently prompted a shift toward Ecological Intensification (EI) practices, aiming to harmonize agricultural productivity and environmental conservation. Despite the benefits of EI, its implementation has been limited, as farmers face challenges in business reorganization and supply chain adaptation. This paper investigates the role of contract farming (CF) in promoting the adoption of sustainable practices among Italian wheat producers. Specifically, it analyzes the influence of farmers’ entrepreneurial identity on their engagement in such initiatives.MethodsUsing the case study of Barilla Group’s Carta del Mulino initiative, an innovative contract farming scheme incentivizing sustainable EI practices, the study explores the relationship between entrepreneurial identity and participation in CF schemes supporting EI. Data from a sample of 314 soft wheat farmers in four regions of Northern Italy were collected to examine the role of entrepreneurial identity in the adoption of sustainable practices and participation in CF schemes. To evaluate the research hypotheses, two distinct econometric models were developed.Results and discussionThe findings reveal that farmers with a more developed entrepreneurial identity are more likely to adopt more sustainable agricultural practices and engage in contractual schemes involving EI practices. The study highlights the importance of fostering and supporting farmers’ entrepreneurial identity while increasing their knowledge of alternative agricultural techniques to address the challenges of the agricultural sector. This integration of individual perspectives (entrepreneurial identity) with a systems view (contract farming schemes) offers valuable insights for future research, policy, and practice in agri-food systems sustainability.

Abstract PIDD1 encodes p53-Induced Death Domain protein 1, which acts as a sensor surveilling centrosome numbers and p53 activity in mammalian cells. Early results also suggest a role in DNA damage response where PIDD1 may act as a cell-fate switch, through interaction with RIP1 and NEMO/IKKg, activating NF-κB signaling for survival, or as an apoptosis-inducing protein by activating caspase-2. Biallelic truncating mutations in CRADD—the protein bridging PIDD1 and caspase-2—have been reported in intellectual disability (ID), and in a form of lissencephaly. Here, we identified five families with ID from Iran, Pakistan, and India, with four different biallelic mutations in PIDD1, all disrupting the Death Domain (DD), through which PIDD1 interacts with CRADD or RIP1. Nonsense mutations Gln863* and Arg637* directly disrupt the DD, as does a missense mutation, Arg815Trp. A homozygous splice mutation in the fifth family is predicted to disrupt splicing upstream of the DD, as confirmed using an exon trap. In HEK293 cells, we show that both Gln863* and Arg815Trp mutants fail to co-localize with CRADD, leading to its aggregation and mis-localization, and fail to co-precipitate CRADD. Using genome-edited cell lines, we show that these three PIDD1 mutations all cause loss of PIDDosome function. Pidd1 null mice show decreased anxiety, but no motor abnormalities. Together this indicates that PIDD1 mutations in humans may cause ID (and possibly lissencephaly) either through gain of function or secondarily, due to altered scaffolding properties, while complete loss of PIDD1, as modeled in mice, may be well tolerated or is compensated for.

Médicos, enfermeiros e outros profissionais de saúde passam boa parte do tempo se comunicando e coordenando atividades de cuidado. Apesar disso, o treinamento em habilidades de comunicação interpessoal e de trabalho em equipe tem sido historicamente pouco enfatizado. O principal objetivo do trabalho em equipe é melhorar os desfechos no cuidado ao paciente. A necessidade de trabalhar em equipe vem sendo cada vez mais frequente no cuidado à saúde. Assim, é relevante conhecer os elementos fundamentais para o seu bom funcionamento, assim como os principais fatores com potencial de prejudicá-lo. Neste artigo, os seguintes tópicos serão discutidos: classificação das equipes de cuidado à saúde; princípios determinantes para o sucesso das equipes; e as principais barreiras que podem comprometer seu funcionamento. Existe um reconhecimento crescente sobre a importância do trabalho em equipe (em oposição ao rígido gerenciamento hierárquico) no cuidado ao paciente. A resistência à mudança nos métodos de trabalho imposta pela tradição de décadas deve ser enfrentada por meio de um processo educacional, de forma que este artigo visa a contribuir para essa finalidade.

This study explores the intersection role of students' epistemic beliefs and gender in argumentative essay writing. In total, 148 undergraduate students from a Dutch university followed an argumentation module, filled out the epistemic beliefs survey, and wrote an argumentative essay. Results showed that students' beliefs about the Internet-specific justification of knowledge did not influence essay performance. On the other hand, beliefs about the nature of scientific knowledge influenced their argumentative essay writing. Overall, there were no gender differences in argumentative essay writing. However, female students outperformed male students in taking a position on the topic. The interaction effects of beliefs about the Internet-specific justification of knowledge and gender in argumentation performance were neutral. There was, however, an intersection effect of students' epistemic beliefs about the nature of scientific knowledge and their gender in argumentation performance. We discuss these results and provide suggestions for future research.

In the light of urgent global sustainability challenges, vocational education is searching for new approaches that are more just and future proof. At least a part of the answer seems to lie in so-called collaborative learning arrangements where students together with societal actors explore sustainability-related challenges. The amount of this kind of arrangements in which vocational education participates increases. Empirical studies on what actually goes on in the collaborative arrangements are rather scarce. This study addresses the theory-practice gap by applying a participatory design. The study unveils that deeply seated educational and socio-cultural routines like the student as learner, alienation from issues, a bias towards cognitive knowing and 'solving' problems seem to limit the possibilities for more genuine collaboration to emerge. The study also found that by intervening with creative and reflexive methods, space for transformative learning can unfold that allows engagement with existential questions like 'what is it what I really got to do here?'. The opening up of these spaces was accompanied by longings to go beyond the rosy narratives of collaborative learning arrangements and to have more attention for the persistent embeddedness of educational routines in the societal issues around us. Vocational education "as" society. What happens if we progress towards vocational education for sustainable futures with more modesty and introspection?

In response to challenges emerging in society, universities are searching for ways to innovate their courses through novel institutional educational policies and practices. Those efforts, however, are often not informed by knowledge about course innovation characteristics university-wide, and are often not supported by processes of reflection questioning the 'who', 'how' and 'for what' of course innovations. This study applied the multifaceted analytical Course Innovation Framework (CIF) in order to explore characteristics of a large set of intended course innovations in a higher education institution in the Netherlands. The application of the CIF enabled a descriptive analysis of multiple characteristics of the intended course innovations. This analysis unveiled university-wide course innovation trends, upon which university stakeholders reflected in order to responsibly guide and transform policy and practices. The study findings show how the application of the CIF helps to gather situated knowledge on university-wide innovation trends, and how reflection on these trends empowers stakeholders to deliberate the culture and values of educational innovation they wish to promote within their institution.

Questo articolo descrive un’esperienza di apprendimento collaborativo in rete, promossa dal CEFPAS – Centro per la Formazione e l’Aggiornamento del Personale Sanitario – in collaborazione con l’Assessorato Regionale della Salute e il Centro Regionale per la Segnalazione Spontanea Organizzata. Il progetto ha previsto l’avvio della Comunità di Pratica on line di Infermieri Siciliani, denominata Community Infermieri 2.0, accreditata per la prima volta nell’ambito del sistema di Educazione Continua in Medicina (ECM). Al fine di valutare se la Community Infermieri 2.0, a cui hanno preso parte 156 operatori siciliani, è uno strumento di apprendimento efficace, un’attenzione particolare è stata dedicata all’analisi quali-quantitativa delle interazioni on line. L’esperienza ha confermato che la Community - risultato di una scelta strategica che coniuga il buon uso della tecnologia e l’impiego di risorse umane specializzate a supporto (tutor metodologici e di processo) - è un valido strumento di apprendimento per la costruzione di attività di cooperazione e collaborazione.

When the compounds are heated in an inert atmosphere it can be verified the consecutive partial sublimation, fusion, partial volatilization and partial thermal decomposition of the anhydrous complexes. When in an oxidating atmosphere the above process is only verified to Cu(II) chelates. Anhydrous copper(II) complexes present a monoclinic structure in the b form and the volatilized compound in a a form. Zinc(II) and cadmium(II) hydrated complexes are isomorphous and they present different cell dimensions from those reported previously.

ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein.

Ankrd2 (also known as Arpp) together with Ankrd1/CARP and DARP are members of the MARP mechanosensing proteins that form a complex with titin (N2A)/calpain 3 protease/myopalladin. In muscle, Ankrd2 is located in the I-band of the sarcomere and moves to the nucleus of adjacent myofibers on muscle injury. In myoblasts it is predominantly in the nucleus and on differentiation shifts from the nucleus to the cytoplasm. In agreement with its role as a sensor it interacts both with sarcomeric proteins and transcription factors.Expression profiling of endogenous Ankrd2 silenced in human myotubes was undertaken to elucidate its role as an intermediary in cell signaling pathways. Silencing Ankrd2 expression altered the expression of genes involved in both intercellular communication (cytokine-cytokine receptor interaction, endocytosis, focal adhesion, tight junction, gap junction and regulation of the actin cytoskeleton) and intracellular communication (calcium, insulin, MAPK, p53, TGF-β and Wnt signaling). The significance of Ankrd2 in cell signaling was strengthened by the fact that we were able to show for the first time that Nkx2.5 and p53 are upstream effectors of the Ankrd2 gene and that Ankrd1/CARP, another MARP member, can modulate the transcriptional ability of MyoD on the Ankrd2 promoter. Another novel finding was the interaction between Ankrd2 and proteins with PDZ and SH3 domains, further supporting its role in signaling. It is noteworthy that we demonstrated that transcription factors PAX6, LHX2, NFIL3 and MECP2, were able to bind both the Ankrd2 protein and its promoter indicating the presence of a regulatory feedback loop mechanism.In conclusion we demonstrate that Ankrd2 is a potent regulator in muscle cells affecting a multitude of pathways and processes.

Purpose: By envisioning the learning environment as an eco-social system, this study aims to map interrelated enablers of students' sustainability-oriented learning (SoL) in the context of a university course at the interface of science and society. Design/methodology/approach: A case-study approach was used to delineate what enables student learning in a university-wide transdisciplinary Master of Science course. A sample of 102 students, university and societal stakeholders participated to this study, by sharing their experiences and views through focus groups and questionnaires. Findings: A main finding is the development of a configuration of six intertwined enablers that through their interplay help to cultivate students' SoL, in the course under exploration. Originality/value: This study paves the way for a re-orientation of how to explore learning in complex environments. It shows that adopting a relational, situated and systems approach is not only feasible but is also desirable to understand and guide learning practices in complex environments.

This paper presents a multi-faceted analytical Course Innovation Framework (CIF) that can help institutes of higher education analyze multiple aspects of course innovation. The CIF was constructed by integrating insights from literature, policy documentation and course-innovation practices at Wageningen University and Research in the Netherlands. The resulting CIF considers multiple stages of course innovation -- intended, implemented and attained -- along with multiple innovation processes organized into the following five clusters: Rationale for the Innovation; Nature of the Innovation; Innovation in Teaching and Learning; Evaluation and Dissemination Strategy; and Consistency and Reflection. University stakeholders experienced the CIF as usable and relevant. This study is intended to generate a multi-faceted understanding of course innovation and to provide university policy-makers and educators with inspiration or even guidance in their efforts to analyze, map and decide upon their course-innovation practices.

AbstractWhile environmental problems are urgent in modern society, they are especially difficult to tackle because of their normative and politically controversial nature. Universities may choose different theoretical paradigms for the teaching of environmental problems. However, limited theoretical and/or practical analysis has been undertaken of the theoretical and normative paradigms underlying education on environmental problems. How do we know if educational approaches sufficiently equip students to deal with environmental issues? This article provides a taxonomy for mapping both environmental paradigms and learning outcomes, allowing for a thematic content analysis of the programs of a Dutch university that focuses on environmental problems. The main findings are that, while the course guides are overall highly internally coherent, there are disciplinary silos where the different disciplines teach from different paradigmatic presuppositions. Furthermore, the programs are very cognitive-centered, leaving little room for affective, social, and behavioral learning outcomes, despite the importance of these in higher education. This cognitive bias is relevant for all paradigmatic outlooks, but especially for the more mechanistically oriented paradigms. While understandable from the substance of these paradigms, multimodality in pedagogy and learning outcomes is needed for a comprehensive education. [ABSTRACT FROM AUTHOR]

There is an urgent need to address the grand sustainability challenges of our time, and to explore new and more responsible ways of operating, researching, and innovating that enable society to respond to these challenges. The emergent Responsible Research and Innovation (RRI) policy agenda can act as a catalyst towards the development of new and more responsible research and innovation efforts. Inevitably, higher education needs to be closely attuned to this need and agenda, by preparing students to engage in RRI efforts. This paper makes a first step towards guiding the embedding of RRI within higher education. It does so by bringing together academic knowledge with phronesis or practical knowledge about what should be done in an ethical, political, and practical sense. It draws on a literature review and on the reflective practices of partners in the European Commission funded project EnRRICH (Enhancing Responsible Research and Innovation through Curricula in Higher Education), as well as on interviews and case studies gathered as part of the project. The paper suggests elements, especially design principles and a competence framework, for (re)designing curricula and pedagogies to equip higher education students to be and to become responsible actors, researchers, and innovators in a complex world, and to address grand sustainability challenges. In addition, this paper proposes that contemporary higher education teaching and learning policies and strategies, especially those promoting neoliberal agendas and marketized practices, need to adopt a more responsible and responsive ethos to foster the renewal of higher education in times of systemic dysfunction.

Autophagy engulfs cellular components in double-membrane-bound autophagosomes for clearance and recycling after fusion with lysosomes. Thus, autophagy is a key process for maintaining proteostasis and a powerful cell-intrinsic host defense mechanism, protecting cells against pathogens by targeting them through a specific form of selective autophagy known as xenophagy. In this context, ubiquitination acts as a signal of recognition of the cargoes for autophagic receptors, which direct them towards autophagosomes for subsequent breakdown. Nevertheless, autophagy can carry out a dual role since numerous viruses including members of the Orthoherpesviridae family can either inhibit or exploit autophagy for its own benefit and to replicate within host cells. There is growing evidence that Herpes simplex virus type 1 (HSV-1), a highly prevalent human pathogen that infects epidermal keratinocytes and sensitive neurons, is capable of negatively modulating autophagy. Since the effects of HSV-1 infection on autophagic receptors have been poorly explored, this study aims to understand the consequences of HSV-1 productive infection on the levels of the major autophagic receptors involved in xenophagy, key proteins in the recruitment of intracellular pathogens into autophagosomes. We found that productive HSV-1 infection in human neuroglioma cells and keratinocytes causes a reduction in the total levels of Ub conjugates and decreases protein levels of autophagic receptors, including SQSTM1/p62, OPTN1, NBR1, and NDP52, a phenotype that is also accompanied by reduced levels of LC3-I and LC3-II, which interact directly with autophagic receptors. Mechanistically, we show these phenotypes are the result of xenophagy activation in the early stages of productive HSV-1 infection to limit virus replication, thereby reducing progeny HSV-1 yield. Additionally, we found that the removal of the tegument HSV-1 protein US11, a recognized viral factor that counteracts autophagy in host cells, enhances the clearance of autophagic receptors, with a significant reduction in the progeny HSV-1 yield. Moreover, the removal of US11 increases the ubiquitination of SQSTM1/p62, indicating that US11 slows down the autophagy turnover of autophagy receptors. Overall, our findings suggest that xenophagy is a potent host defense against HSV-1 replication and reveals the role of the autophagic receptors in the delivery of HSV-1 to clearance via xenophagy. [ABSTRACT FROM AUTHOR]

This study explores the intersection role of students' epistemic beliefs and gender in argumentative essay writing. In total, 148 undergraduate students from a Dutch university followed an argumentation module, filled out the epistemic beliefs survey, and wrote an argumentative essay. Results showed that students' beliefs about the Internet-specific justification of knowledge did not influence essay performance. On the other hand, beliefs about the nature of scientific knowledge influenced their argumentative essay writing. Overall, there were no gender differences in argumentative essay writing. However, female students outperformed male students in taking a position on the topic. The interaction effects of beliefs about the Internet-specific justification of knowledge and gender in argumentation performance were neutral. There was, however, an intersection effect of students' epistemic beliefs about the nature of scientific knowledge and their gender in argumentation performance. We discuss these results and provide suggestions for future research. [ABSTRACT FROM AUTHOR]

Background: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health. Methods: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants' experiences, thoughts, expectations and attitudes. Results: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis. Conclusion: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support. [ABSTRACT FROM AUTHOR]

Purpose: While empowerment for sustainability is considered a major objective within sustainability-oriented educational programs and policies, little is known about the actual process of empowering students for sustainability through higher education. This study aims to explore this field, by introducing the EYE (Educating Yourself in Empowerment) for Sustainability learning tool and by analyzing the effects of its application within a higher education context, including a reflection about key aspects contributing to students' empowerment for sustainability. Design/methodology/approach: The effects of the EYE tool are analyzed by means of questionnaires. Through a qualitative codification process and quantitative analysis, the authors have reflected on the effects of the EYE tool and on the empowerment process as perceived by the students exposed to the EYE at Wageningen University. Findings: Results suggest that the EYE is a comprehensive and adaptive tool, conducive to empowerment for sustainability. Adopting, only partly, an instrumental approach to education and, largely, an emancipatory one appears to be a possible and successful combination. A key aspect contributing to students' empowerment for sustainability is the development and execution of a real-life project of own choice. Learning about the diverse worldviews underlying the search for sustainability appears to be an eye opener for the students. Empowerment does not seem to require long-term training. Rather, it emerges and is experienced by university students within a few weeks. Originality/value: This paper introduces a novel tool and discusses insights deriving from the application of this tool. The value of the paper lies in its potential to support educators in reflecting upon and designing their educational strategy for empowering students for sustainability.

In the light of urgent global sustainability challenges, vocational education is searching for new approaches that are more just and future proof. At least a part of the answer seems to lie in so-called collaborative learning arrangements where students together with societal actors explore sustainability-related challenges. The amount of this kind of arrangements in which vocational education participates increases. Empirical studies on what actually goes on in the collaborative arrangements are rather scarce. This study addresses the theory-practice gap by applying a participatory design. The study unveils that deeply seated educational and socio-cultural routines like the student as learner, alienation from issues, a bias towards cognitive knowing and 'solving' problems seem to limit the possibilities for more genuine collaboration to emerge. The study also found that by intervening with creative and reflexive methods, space for transformative learning can unfold that allows engagement with existential questions like 'what is it what I really got to do here?'. The opening up of these spaces was accompanied by longings to go beyond the rosy narratives of collaborative learning arrangements and to have more attention for the persistent embeddedness of educational routines in the societal issues around us. Vocational education as society. What happens if we progress towards vocational education for sustainable futures with more modesty and introspection? [ABSTRACT FROM AUTHOR]

In response to challenges emerging in society, universities are searching for ways to innovate their courses through novel institutional educational policies and practices. Those efforts, however, are often not informed by knowledge about course innovation characteristics university-wide, and are often not supported by processes of reflection questioning the 'who', 'how' and 'for what' of course innovations. This study applied the multifaceted analytical Course Innovation Framework (CIF) in order to explore characteristics of a large set of intended course innovations in a higher education institution in the Netherlands. The application of the CIF enabled a descriptive analysis of multiple characteristics of the intended course innovations. This analysis unveiled university-wide course innovation trends, upon which university stakeholders reflected in order to responsibly guide and transform policy and practices. The study findings show how the application of the CIF helps to gather situated knowledge on university-wide innovation trends, and how reflection on these trends empowers stakeholders to deliberate the culture and values of educational innovation they wish to promote within their institution. [ABSTRACT FROM AUTHOR]